Remodeling Osteoarthritic Articular Cartilage under Hypoxic Conditions.
Mohd Heikal Mohd YunusYemin LeeAbid NordinKien Hui ChuaRuszymah Bt Hj IdrusPublished in: International journal of molecular sciences (2022)
Osteoarthritis (OA) is one of the leading joint diseases induced by abnormalities or inflammation in the synovial membrane and articular cartilage, causing severe pain and disability. Along with the cartilage malfunction, imbalanced oxygen uptake occurs, changing chondrocytes into type I collagen- and type X collagen-producing dedifferentiated cells, contributing to OA progression. However, mounting evidence suggests treating OA by inducing a hypoxic environment in the articular cartilage, targeting the inhibition of several OA-related pathways to bring chondrocytes into a normal state. This review discusses the implications of OA-diseased articular cartilage on chondrocyte phenotypes and turnover and debates the hypoxic mechanism of action. Furthermore, this review highlights the new understanding of OA, provided by tissue engineering and a regenerative medicine experimental design, modeling the disease into diverse 2D and 3D structures and investigating hypoxia and hypoxia-inducing biomolecules and potential cell therapies. This review also reports the mechanism of hypoxic regulation and highlights the importance of activating and stabilizing the hypoxia-inducible factor and related molecules to protect chondrocytes from mitochondrial dysfunction and apoptosis occurring under the influence of OA.
Keyphrases
- knee osteoarthritis
- tissue engineering
- oxidative stress
- cell cycle arrest
- extracellular matrix
- induced apoptosis
- cell death
- rheumatoid arthritis
- endothelial cells
- multiple sclerosis
- endoplasmic reticulum stress
- cell therapy
- high resolution
- cancer therapy
- risk assessment
- wound healing
- pain management
- early onset
- human health
- cell proliferation
- body composition
- drug induced
- mesenchymal stem cells
- pi k akt
- adverse drug